Enhanced follicular dendritic cell function in lymph nodes of simian immunodeficiency virus-infected macaques: consequences for pathogenesis.
HIV and simian immunodeficiency virus (SIV) infections are characterized by several abnormalities in B cell function. Pathogenesis is also associated with marked changes within germinal centers (GC) including hypertrophy and degeneration of follicular dendritic cells (FDC) and accumulation of both viral antigen and activated CD45RO+ CD8+ cells. Since FDC are critical to the generation of antibody-forming cells and specific B cell memory, the simplest assumption is that such B cell defects directly result from virus-induced changes in the GC environment. The present study examined FDC-enriched mesenteric lymph node lymphocyte preparations from early and late stage SIV-infected and uninfected macaques for their ability to support GC reactions in vitro. The results indicate that FDC function as measured by cluster formation, B cell proliferation and SIV-specific antibody production is enhanced in SIV-infected macaques suggesting that, despite FDC atrophy, virus accumulation induces increased FDC-B cell interactions resulting in B cell hyperactivity. The activation and proliferation of CD8+ cells in FDC-enriched cultures further suggest that the infiltrating CD8+ population observed in situ in GC of late-stage SIV/HIV-infected individuals may also benefit from FDC-derived growth signals. Thus, in addition to enhanced B cell proliferation and antibody production, hyperactivity of FDC may potentially promote their own self destruction via the infiltrating CD8+ cells. The increased B cell responsiveness may further exacerbate the disease process due to an overall decrease in the affinity of anti-HIV/SIV antibody, a loss of crucial protective antibodies to other infectious agents and the creation of an environment in which increased trapping of virions facilitates more extensive infection of CD4+ T cells.
Rosenberg
Y J
YJ
Therimmune Inc., Rockville, MD, USA.
Lewis
M G
MG
Greenhouse
J J
JJ
Cafaro
A
A
Leon
E C
EC
Brown
C R
CR
Bieg
K E
KE
Kosco-Vilbois
M H
MH
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008213:Lymphocyte Activation; D008251:Macaca; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000473:pathology; D015302:Simian Immunodeficiency Virus